Use of Bone Allograft With or Without Bone Marrow Aspirate Concentrate in Appositional Reconstructions: A Tomographic and Histomorphometric Study.
To evaluate bone allograft associated to bone marrow aspirate concentrate (BMAC), in maxillary reconstructions. Ten patients with alveolar bone deficiency in the anterior maxilla were randomly divided into control group (CG) and test group (TG). A bone block allograft was placed in both groups, but the graft was impregnated with BMAC only in TG. Computed tomography was performed 7 days (T1) and 6 months (T2) after the grafting procedure, and volume and bone density measurements were carried out. Histomorphometric analysis was performed at T2. Bone volume loss from T1 to T2 was significant only in TG. The bone density in the buccal region of the graft was significantly higher in TG than in CG. There was no significant difference between the groups, in respect to mineralized tissue (MT) and nonmineralized tissue (NMT), in that MT values were 37.77% ± 15.19% and 43.85% ± 10.94%, and NMT values were 62.15% ± 14.90% and 56.30% ± 10.72%, respectively, for CG and TG. The intragroup difference for the MT/NMT ratio was statistically significant in CG but not significant in TG. The use of BMAC resulted in an improved pattern of bone formation, with higher bone density in the peripheral regions of the graft.


Improving the Drug Development Pipeline for Mycobacteria: Modelling Antibiotic Exposure in the Hollow Fibre Infection Model.
Mycobacterial infections are difficult to treat, requiring a combination of drugs and lengthy treatment times, thereby presenting a substantial burden to both the patient and health services worldwide. The limited treatment options available are under threat due to the emergence of antibiotic resistance in the pathogen, hence necessitating the development of new treatment regimens. Drug development processes are lengthy, resource intensive, and high-risk, which have contributed to market failure as demonstrated by pharmaceutical companies limiting their antimicrobial drug discovery programmes. Pre-clinical protocols evaluating treatment regimens that can mimic in vivo PK/PD attributes can underpin the drug development process. The hollow fibre infection model (HFIM) allows for the pathogen to be exposed to a single or a combination of agents at concentrations achieved in vivo-in plasma or at infection sites. Samples taken from the HFIM, depending on the analyses performed, provide information on the rate of bacterial killing and the emergence of resistance. Thereby, the HFIM is an effective means to investigate the efficacy of a drug combination. Although applicable to a wide variety of infections, the complexity of anti-mycobacterial drug discovery makes the information available from the HFIM invaluable as explored in this review.


Interplay between modifications of chromatin and meiotic recombination hotspots.
Meiotic recombination lies at the heart of sexual reproduction. It is essential for producing viable gametes with a normal haploid genomic content and its dysfunctions can be at the source of aneuploidies, such as the Down syndrome, or many genetic disorders. Meiotic recombination also generates genetic diversity that is transmitted to progeny by shuffling maternal and paternal alleles along chromosomes. Recombination takes place at non-random chromosomal sites called 'hotspots'. Recent evidence has shown that their location is influenced by properties of chromatin. In addition, many studies in somatic cells have highlighted the need for changes in chromatin dynamics to allow the process of recombination. In this review, we discuss how changes in the chromatin landscape may influence the recombination map, and reciprocally, how recombination events may lead to epigenetic modifications at sites of recombination, which could be transmitted to progeny.


Strain evolution in coherent Ge/Si islands
Strain evolution of coherent Ge islands on Si(001) is measured using a newly developed transmission electron microscopy technique based on two-beam dark-field strain imaging. The strain measurements show that a metastable Ge island shape is involved in the shape transition between pyramids and domes; this shape is more readily observed for growth at 550 than 600 degrees C because of the slower rate at which islands cross the kinetic barrier between shapes. The strain relaxation changes discontinuously between pyramids and domes, indicating that the underlying shape transition is first order.


Coxiella burnetii total immunoglobulin G, phase I and phase II immunoglobulin G antibodies, and bacterial shedding in young dams in persistently infected dairy herds.
The current study examines Coxiella burnetii infection patterns in young dairy dams around the calving period in persistently infected high-producing dairy herds. Infection patterns were determined in terms of total immunoglobulin G (IgG) and phase-specific IgG antibodies by enzyme-linked immunosorbent assay and bacterial shedding by real-time polymerase chain reaction (qPCR). On days 171-177 of gestation, at parturition, and on days 15-21 and 91-97 postpartum, 7 first-parity cows and 7 second-parity cows were sampled for serology and qPCR. Total phase-specific I (PhI) and II (PhII) IgG antibodies were detected in 2 animals at days 171-177 of gestation. Four additional animals underwent seroconversion on days 91-97 postpartum. Three of 6 seropositive dams according to total IgG, showed a PhI+/PhII+ profile, whereas dams that seroconverted exhibited a PhI-/PhII+ (2/6) or PhI+/PhII- (1/6) profile. An indirect fluorescent antibody test for PhI and PhII immunoglobulin M (IgM) was performed on plasma samples from the shedding dams, confirming seropositivity in a first-parity dam that seroconverted, and detecting a sudden spike of PhI-IgM antibodies in 1 further dam. No relationship was detected in young C. burnetii-infected animals between total IgG, PhI and/or PhII antibodies, and bacterial shedding throughout the study period. The highest bacterial load measured by qPCR was recorded in a second-parity dam. This animal presented abnormal peripheral blood counts, which would be an indication of severe peripheral blood alterations in some infected cattle. This study suggests that young shedder cows are mostly seronegative in early stages of infection.


Host behaviour and exposure risk in an insect-pathogen interaction.
1. Studies of variability in host resistance to disease generally emphasize variability in susceptibility given exposure, neglecting the possibility that hosts may vary in behaviours that affect the risk of exposure. 2. In many insects, horizontal transmission of baculoviruses occurs when larvae consume foliage contaminated by the cadavers of virus-infected conspecific larvae; so, host behaviour may have a strong effect on the risk of infection. 3. We studied variability in the behaviour of gypsy moth (Lymantria dispar) larvae, which are able to detect and avoid virus-contaminated foliage. 4. Our results show that detection ability can be affected by the family line that larvae originate from, even at some distance from a virus-infected cadaver, and suggest that cadaver-detection ability may be heritable. 5. There is thus the potential for natural selection to act on cadaver-detection ability, and thereby to affect the dynamics of pathogen-driven cycles in gypsy moth populations. 6. We argue that host behaviour is a neglected component in studies of variability in disease resistance.


Seeing the forest through the trees: differential dispersal of Hylobius warreni within modified forest habitats.
Hylobius warreni Wood, also known as the Warren root collar weevil, is a flightless insect that feeds on conifers throughout the boreal forests of Canada. Mature trees typically can withstand feeding, but larval feeding around the root collar may cause mortality to young trees. Recently, a large outbreak of mountain pine beetle (Dendroctonus ponderosae Hopkins) has killed a high proportion of mature lodgepole pine (Pinus contorta Douglas variety latifolia) across British Columbia, Canada. This raises concerns that adult weevils may migrate from mature forests with reduced host pools into adjacent young forests that had been salvaged and replanted. To study movement of these walking weevils in different habitat types, we constructed three research plots consisting of various combinations of live-, dead-, and mixed (i.e., live and dead)-tree habitats. We observed dispersal patterns of individually labeled insects using a novel insect trap attached to the base of trees. Approximately 35% of insects were recaptured over 1 mo. Weevils were least likely to be recaptured proximate to the release location when released in a habitat with dead trees. Movement rates therein were almost double the rates of insects moving through live- or mixed-tree habitats. Our findings support the hypothesis that H. warreni may disperse out of habitats with dead trees into areas with higher proportions of green trees. Our findings are discussed in the context of habitat discrimination and potential increases in herbivory by H. warreni in western Canada given salvage harvesting activities after outbreaks of mountain pine beetle.


[Salmonella enteritidis osteomyelitis of the tibia--a case report and review of literature on Salmonella osteomyelitis of Japanese patients].
We described a rare case of Salmonella enteritidis osteomyelitis of the tibia combined with arthritis of the ankle joint. A 4-year-old, otherwise healthy girl was hospitalized with 9-day history of fever, left leg pain, and diarrhea. On admission, her left lower leg and ankle were markedly reddened and swollen. Laboratory examinations disclosed a WBC of 16,300/microliter and a C-reactive protein of 15.6 mg/dl. A T2-weighed magnetic resonance image of the leg depicted a high intensity area around the left distal tibia and an extremely high intensity fluid in her left ankle joint, leading to our diagnosis of purulent osteomyelitis of the tibia and arthritis of the ankle joint. Salmonella enteritidis was isolated from ankle joint fluid and later aspirated bone marrow of the tibia, but not from blood or stool. Because of poor response to intravenous treatment with panipenem/betamipron for 2 days, she underwent drainage and washing of the joint fluid, and intramedullary administration of cefotaxime and ampicillin. She completely recovered without sequelae following treatment with sensitive antibiotics for 4 weeks in total. There has not been any relapse for more than 1.5 years. The authors also bibliographically surveyed the literature published from 1966 to 2002 and found 35 Japanese patients with Salmonella osteomyelitis. The present patient was the second case caused by Salmonella enteritidis in Japan. Septic arthritis is a rare complication, accounting for only 8% of the patients. Since Salmonella enteritidis has been a leading serotype among human isolates of Salmonella species during the past decade, it would be warranted to determine whether osteomyelitis due to this organism is likely to increase.


The in vitro effect of three antibiotics on alveolar macrophages.
The effects of 3 antibiotics, azlocillin, ticarcillin and tobramycin, on rat alveolar macrophage function has been examined. These antibiotics are used in the treatment of Pseudomonas aeruginosa lung infections in cystic fibrosis patients. In this study low concentrations of the antibiotics were used, similar to the low levels found in the lungs of these patients. Tobramycin, a highly active aminoglycoside, inhibited the phagocytosis of opsonized Pseudomonas aeruginosa and enhanced the binding of sheep erythrocytes sensitized with IgG2b, when pre-incubated with macrophage monolayers for 30 min. Inhibition of both phagocytosis and binding of sensitized sheep erythrocytes was observed when tobramycin was co-incubated with the macrophage monolayers and indicator cells. Azlocillin, a semi-synthetic penicillin, caused inhibition of phagocytosis of opsonized bacteria and binding of sensitized sheep erythrocytes when added with the indicator cells. However, no effect was found if the macrophages were pre-incubated with azlocillin for 30 min. Ticarcillin, a semi-synthetic penicillin which is less active in vitro as an antimicrobial agent than azlocillin, had no effect on alveolar macrophages at the concentrations used in these assays. It is postulated that if these in vitro findings with rat alveolar macrophages are reflected in the in vivo situation in humans, the effect of antibiotics on host defence may be of clinical importance.


Image-Based Method to Quantify Decellularization of Tissue Sections.
Tissue decellularization is typically assessed through absorbance-based DNA quantification after tissue digestion. This method has several disadvantages, namely its destructive nature and inadequacy in experimental situations where tissue is scarce. Here, we present an image processing algorithm for quantitative analysis of DNA content in (de)cellularized tissues as a faster, simpler and more comprehensive alternative. Our method uses local entropy measurements of a phase contrast image to create a mask, which is then applied to corresponding nuclei labelled (UV) images to extract average fluorescence intensities as an estimate of DNA content. The method can be used on native or decellularized tissue to quantify DNA content, thus allowing quantitative assessment of decellularization procedures. We confirm that our new method yields results in line with those obtained using the standard DNA quantification method and that it is successful for both lung and heart tissues. We are also able to accurately obtain a timeline of decreasing DNA content with increased incubation time with a decellularizing agent. Finally, the identified masks can also be applied to additional fluorescence images of immunostained proteins such as collagen or elastin, thus allowing further image-based tissue characterization.


Protozoal parasites in tick species infesting camels in Sinai Peninsula.
A faunistic survey of ticks infesting camels was carried out in 7 localities of Sinai; El-Arish, Beer El Abd, Nakhel, Ain Mousa, St. Catherine, Wadi Hadra, and Dahab. The protozoal organisms present in the gut and haemolymph of the collected tick species were investigated. Results revealed the presence of six species of tick infesting camels, Hyalomma dromedarii, H. impeltatum, H. an. excavatum, H. an. anatolicum, H. marginatum and H. schulzei. The first 3 species were most common, whereas the latter 3 species were found in certain limited localities. Babesia sp. and Theilera sp. were recorded in both tick guts and haemolymph in most species allover the studied areas. Trypanosoma sp. was recorded in the guts of ticks collected from Beer El Abd, Nakhel and Dahab. Anaplasma sp. was found in tick guts from Beer El Abd and Dahab, however the same organism was detected in the haemolymph of ticks collected in Nakhel and Dahab.


Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2).
Prostate cancer is the most common malignancy in males and is the second most common cause of cancer mortality in American men. Polymorphisms have been identified in two genes, the 17-hydroxylase cytochrome P450 gene (CYP17) and the steroid 5-reductase type II gene (SRD5A2) that are involved with androgen biosynthesis and metabolism. The CYP17 A2 allele contains a T-->C transition in the 5' promoter region that creates an additional Sp1-type (CCACC box) promoter site. The SRD5A2 valine to leucine (V89L) polymorphism has been correlated with lower dihydroxytestosterone levels. We tested genotypes in 108 prostate cases and 167 controls along with samples (n = 340) from several different ethnic groups. The CYP17 A2 allele (combined A1/A2 and A2/A2 genotypes) occurred at a higher frequency in Caucasian patients with prostate cancer (70%) than in Caucasian clinical control urology patients (57%), suggesting that the A2 allele may convey increased risk for prostate cancer [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.0-3.0]. Blacks and Caucasians had a similar frequency of the A2 genotype (16 and 17%, respectively) while Taiwanese had the highest frequency (27%). The SRD5A2 leucine genotype was most frequent in Taiwanese (28%), intermediate in Caucasians (8.5%) and lowest in Blacks (2.5%). Genotypes having a SRD5A2 leucine allele were somewhat more common in prostate cancer cases (56%) than in controls (49%) (OR = 1.4, 95% CI = 0.8-2.2) but this difference was not significant. These results support the hypothesis that some allelic variants of genes involved in androgen biosynthesis and metabolism may be associated with prostate cancer risk.


VISGRADER: Automatic Grading of D3 Visualizations.
Manually grading D3 data visualizations is a challenging endeavor, and is especially difficult for large classes with hundreds of students. Grading an interactive visualization requires a combination of interactive, quantitative, and qualitative evaluation that are conventionally done manually and are difficult to scale up as the visualization complexity, data size, and number of students increase. We present VISGRADER, a first-of-its kind automatic grading method for D3 visualizations that scalably and precisely evaluates the data bindings, visual encodings, interactions, and design specifications used in a visualization. Our method enhances students' learning experience, enabling them to submit their code frequently and receive rapid feedback to better inform iteration and improvement to their code and visualization design. We have successfully deployed our method and auto-graded D3 submissions from more than 4000 students in a visualization course at Georgia Tech, and received positive feedback for expanding its adoption.


A simple approach to measure transmissibility and forecast incidence.
Outbreaks of novel pathogens such as SARS, pandemic influenza and Ebola require substantial investments in reactive interventions, with consequent implementation plans sometimes revised on a weekly basis. Therefore, short-term forecasts of incidence are often of high priority. In light of the recent Ebola epidemic in West Africa, a forecasting exercise was convened by a network of infectious disease modellers. The challenge was to forecast unseen "future" simulated data for four different scenarios at five different time points. In a similar method to that used during the recent Ebola epidemic, we estimated current levels of transmissibility, over variable time-windows chosen in an ad hoc way. Current estimated transmissibility was then used to forecast near-future incidence. We performed well within the challenge and often produced accurate forecasts. A retrospective analysis showed that our subjective method for deciding on the window of time with which to estimate transmissibility often resulted in the optimal choice. However, when near-future trends deviated substantially from exponential patterns, the accuracy of our forecasts was reduced. This exercise highlights the urgent need for infectious disease modellers to develop more robust descriptions of processes - other than the widespread depletion of susceptible individuals - that produce non-exponential patterns of incidence.


Improved glucose tolerance in mice receiving intraperitoneal transplantation of normal fat tissue.
The association between increased (visceral) fat mass, insulin resistance and type 2 diabetes mellitus is well known. Yet, it is unclear whether the mere increase in intra-abdominal fat mass, or rather functional alterations in fat tissue in obesity contribute to the development of insulin resistance in obese patients. Here we attempted to isolate the metabolic effect of increased fat mass by fat tissue transplantation. Epididymal fat pads were removed from male C57Bl6/J mice and transplanted intraperitoneally into male littermates (recipients), increasing the combined perigonadal fat mass by 50% (p < 0.005). At 4 and 8 weeks post-transplantation, glucose and insulin tolerance tests were performed, and insulin, NEFA and adipokines measured. Circulating levels of NEFA, adiponectin and leptin were not significantly different between transplanted and sham-operated control mice, while results of the postprandial insulin tolerance test were similar between the two groups. In contrast, under fasting conditions, the mere increase in intra-abdominal fat mass resulted in decreased plasma glucose levels (6.9 +/- 0.4 vs 8.1 +/- 0.3 mmol/l, p = 0.03) and a approximately 20% lower AUC in the glucose tolerance test (p = 0.02) in transplanted mice. Homeostasis model assessment of insulin resistance (HOMA-IR) was 4.1 +/- 0.4 in transplanted mice (vs 6.2 +/- 0.7 in sham-operated controls) (p = 0.02), suggesting improved insulin sensitivity. Linear regression modelling revealed that while total body weight positively correlated, as expected, with HOMA-IR (beta: 0.728, p = 0.006), higher transplanted fat mass correlated with lower HOMA-IR (beta: -0.505, p = 0.031). Increasing intra-abdominal fat mass by transplantation of fat from normal mice improved, rather than impaired, fasting glucose tolerance and insulin sensitivity, achieving an effect opposite to the expected metabolic consequence of increased visceral fat in obesity.


Effects of acute hypoglycemia on the orexin system in rat.
To evaluate the effects of acute glucose level changes on expression of prepro-orexin, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) mRNA in rat hypothalamus tissue and pancreatic islets cells. Thirty adult male Wistar rats were randomly divided into three equal groups (n = 10). The acute hypoglycemia rat model was induced by a single subcutaneous injection of insulin. Twenty acute hypoglycemia rats were divided into group B and group C. Group B was allowed to eat freely, while group C was food-deprived. Control rats were injected the same volume of saline. The effect of glucose levels (2.8 mmol/L and 8.3 mmol/L) on pancreatic islet cell orexin system was detected in pancreas islet cell cultured in vitro. The expression of prepro-orexin and OXR mRNA was examined in rat hypothalamus tissue and pancreatic islets cell cultured in vitro using reverse transcription-polymerase chain reaction (RT-PCR). Expression of orexin mRNA increased about 150% for the food-deprived hypoglycemia rats in comparison with control group (P < 0.01), whereas expression of OX1R mRNA decreased up to 30% (P < 0.01). However, expression of OX2R mRNA was unchanged in comparison with control group. In vitro, after incubation with 2.8 mmol/L glucose for 6 hours, the expression of prepro-orexin mRNA increased 2 times in rat pancreas islet cells in comparison with 8.3 mmol/L glucose group (P < 0.01). But the expression of OX1R mRNA was not sensitive to acute glucose fluctuation. Orexin in rat hypothalamus is stimulated by decline in blood glucose and inhibited by signals related to feeding. Moreover, glucose plays a role in modulating the gene expression of prepro-orexin in rat pancreatic islet cells.


Two mutant forms of the S1/TPR-containing protein Rrp5p affect the 18S rRNA synthesis in Saccharomyces cerevisiae.
The genetic depletion of yeast Rrp5p results in a synthesis defect of both 18S and 5.8S ribosomal RNAs (Venema J, Tollervey D. 1996. EMBO J 15:5701-5714). We have isolated the RRP5gene in a genetic approach aimed to select for yeast factors interfering with protein import into mitochondria. We describe here a striking feature of Rrp5p amino acid sequence, namely the presence of twelve putative S1 RNA-binding motifs and seven tetratricopeptide repeats (TPR) motifs. We have constructed two conditional temperature-sensitive alleles of RRP5 gene and analyzed them for associated rRNA-processing defects. First, a functional "bipartite gene" was generated revealing that the S1 and TPR parts of the protein can act independently of each other. We also generated a two amino acid deletion in TPR unit 1 (rrp5delta6 allele). The two mutant forms of Rrp5p were shown to cause a defect in 18S rRNA synthesis with no detectable effects on 5.8S rRNA production. However, the rRNA processing pathway was differently affected in each case. Interestingly, the ROK1 gene which, like RRP5, was previously isolated in a screen for synthetic lethal mutations with snR10 deletion, was here identified as a high copy suppressor of the rrp5delta6 temperature-sensitive allele. ROK1 also acts as a low copy suppressor but cannot bypass the cellular requirement for RRP5. Furthermore, we show that suppression by the Rok1p putative RNA helicase rescues the 18S rRNA synthesis defect caused by the rrp5delta6 mutation.


In-vivo studies in the treatment of oral ulcers with liposomal dexamethasone sodium phosphate.
Liposomes are man-made organelles composed of bimolecular lipid layers enclosing aqueous compartments. Dexamethasone Sodium Phosphate (DSP) was encapsulated in MLV liposomes and served as the test solution. DSP in solution served as control. Both were labeled with 99mTc. The rats were divided into three groups: typical application group, intramucosal injection and control group. Oral mucosal ulcers were produced by silver nitrate and was monofocal. Rats were killed at three and 24 h, respectively, after application. Ulcerated mucosa, intact adjacent mucosa and distant mucosa were excised. Biodistribution was determined by radiotracer technique in the three mucosal parts as well as in the blood, liver, spleen and brain. Liposomes increase local and decrease systemic drug concentration. Another finding was that liposomes localize the drug in the ulcerated area. In conclusion, liposomes may be useful in the treatment of oral ulcers.


Reward-based decision making and electrodermal responding by young children with autism spectrum disorders during a gambling task.
In this study, we explore reward-based decision making and electrodermal responding (EDR) among children with autism spectrum disorder (ASD) during a children's gambling task. In addition, we examine whether individual behavioral and EDR responses predict social communication, repetitive symptoms, parent reports of executive function, and behavioral challenges. The ability to form advantageous strategies for long-term gain is of interest for children with ASD, who exhibit both difficulty with executive function and atypical responses to reward. Twenty-one children ages 6-7 years with ASD and no intellectual disability, and 21 age- and IQ-matched typically developing children participated. Both groups exhibited a similar pattern of gambling selections, but children with ASD showed less knowledge of the reward contingencies of the decks after playing. In addition, although EDR was similar between groups in anticipation of selections, children with ASD exhibited greater EDR during feedback about rewards as the task progressed. Children with ASD who exhibited the greatest increases in EDR were more likely to exhibit repetitive symptoms, particularly rituals and the need for sameness, as well as internalizing behaviors and reduced executive function in other settings.


Polylactic acid-based microcapsules for moisture-triggered release of chlorine dioxide and its application in cherry tomatoes preservation.
Polylactic acid (PLA)-based microcapsules, capable of releasing chlorine dioxide (ClO2) upon exposure to moisture, have been developed for fruits and vegetables preservation. The microcapsules were prepared by emulsion solvent evaporation, utilizing PLA as the wall material, and NaClO2 as the core material. After optimization, NaClO2 microcapsules exhibited an encapsulation efficiency of 55.75 % and an average particle size of 498.08 μm. Citric acid microcapsules were prepared using the same process, but with citric acid as the core material. When the two kinds of microcapsules were mixed, gaseous ClO2 was released in a highly humid environment. The release rate could be adjusted by temperature and the ratio between the two microcapsules, and the release period could be as long as 17 days at 20 °C. With a certain amount of microcapsules placed in the package of cherry tomatoes, the decay rate and weight loss rate of the fruits were reduced by 63 % and 34 %, respectively, compared to the control group. The microcapsules also helped to maintain the good appearance, hardness, and the content of total soluble solid content and titratable acid content of cherry tomatoes. Therefore, the PLA-based microcapsules have satisfied convenience and effectiveness for application in fruit and vegetables preservation.


Laparoscopic extended (subtotal) distal pancreatectomy with resection of both splenic artery and vein.
Spleen-preserving distal pancreatectomy can be performed safely and effectively by resecting both splenic vessels (Warshaw procedure). This simplified spleen-preserving technique might also be applied to minimally invasive distal pancreatectomy of benign and borderline malignant tumor. Although the conservation of both splenic vessels is paramount to preserving the spleen during laparoscopic distal pancreatectomy, preservation of the splenic vessels is not always possible, especially under the following conditions: (1) relatively large tumor, (2) associated with chronic pancreatitis, (3) tumor abutting splenic vascular structures, and (4) bleeding during the splenic vessel conserving procedure, which are potential indications of laparoscopic extended Warshaw procedure. Patient preparation and position was the same as that described in our previous study. During the study's time period, 38 consecutive patients underwent laparoscopic spleen-preserving distal pancreatectomy. Of those, five patients underwent a laparoscopic extended Warshaw procedure, which all included among 16 patients of extended distal pancreatectomy by dividing the pancreas at the pancreatic neck. All patients were women with a median age of 55 (range, 38-75) years. Median total operation time and blood loss were 215 (range, 200-386) minutes and 100 (range, 0-300) ml, respectively. The median length of hospital stay was 8 (range, 5-15) days. All of postoperative complications (two grade A and two grade B postoperative pancreatic fistula; one grade A bleeding) were able to be treated conservatively. During the median follow-up period of 11 (range, 7-42) months, one focal splenic infarction and one gastric varix were noted; however, no clinically significant complications were reported. Laparoscopic spleen-preserving extended distal pancreatectomy with resection of both the splenic vessels is feasible and safe. This surgical technique is thought to increase the chance of preservation of the spleen with minimally invasive distal pancreatectomy in well-selected benign or borderline malignant tumor of the distal pancreas.


The induction of myeloid leukaemias by Rauscher murine leukaemia virus.
A number of cloned viral preparations isolated from Rauscher virus-producing JLS-V5 cells were compared in their competence to induce different types of leukaemias. All preparations were able to induce myeloid leukaemias, but the induction of lymphatic or erythroid leukaemias was also observed. Serial infection of newborn mice with either cell-free extracts or serum from animals suffering from a myeloid leukaemia did not result in the occurrence of relatively more myeloid leukaemias nor did the infection with virus harvested from ascites fluid of permanent myeloid cell lines. It appears that the mechanism by which myeloid leukaemias are induced is not virus-specific.


Chronic infections of West Nile virus detected in California dead birds.
During 2010 and 2011, 933 recently deceased birds, submitted as part of the dead bird surveillance program, tested positive for West Nile virus RNA at necropsy. The relative amount of RNA measured by qRT-PCR cycles ranged from 8.2 to 37.0 cycle threshold (Ct) and formed a bimodal frequency distribution, with maxima at 20 and 36 Ct and minima at 28-30 Ct. On the basis of frequency distributions among different avian species with different responses to infection following experimental inoculation, field serological data indicating survival of infection, and the discovery of persistent RNA in experimentally infected birds, dead birds collected in nature were scored as "recent" or "chronic" infections on the basis of Ct scores. The percentage of birds scored as having chronic infections was highest during late winter/spring, when all birds were after hatching year, and lowest during late summer, when enzootic transmission was typically highest as indicated by mosquito infections. Our data indicated that intervention efforts should not be based on dead birds with chronic infections unless supported by additional surveillance metrics.


The ditungsten decacarbonyl dianion.
We report the synthesis and structural authentication of the ditungsten decarbonyl dianion in [(OC)5W-W(CO)5][K(18-crown-6)(THF)2]2 (1), completing the group 6 dianion triad over half a century since the area began. The W-W bond is long [3.2419(8) Å] and, surprisingly, in the solid-state the dianion adopts a D4h eclipsed rather than D4d staggered geometry, the latter of which dominates the structural chemistry of binary homobimetallic carbonyls. Computational studies at levels of theory from DFT to CCSD(T) confirm that the D4d geometry is energetically preferred in the gas-phase, being ∼18 kJ mol-1 more stable than the D4h form, since slight destabilisation of the degenerate W-CO π 5dxz and 5dyz orbitals is outweighed by greater stabilisation of the W-W σ-bond orbital. The gas-phase D4h structure displays a single imaginary vibrational mode, intrinsic reaction coordinate analysis of which links the D4h isomer directly to the D4d forms, which are produced by rotation around the W-W bond by ±45°. It is therefore concluded that the gas-phase transition state becomes a minimum on the potential energy surface when subjected to crystal packing in the solid-state.


[Nutrition and health--unclear association between intake of vitamin E and the risk of coronary heart disease].
Vitamin E is a fat-soluble antioxidant and is possibly involved in the prevention of coronary heart disease by inhibiting oxidative modification of LDL cholesterol. The results of studies on the association between vitamin-E intake and coronary heart disease are inconsistent in observational studies and absent in large-scale intervention studies. This may be the consequence of confounding in observational studies and imperfections in the design of intervention trials. Another explanation is that vitamin E may only function protectively in the presence of sufficient co-antioxidants. At present, there is no evidence that vitamin E lowers the risk of coronary heart disease.


Relationship of the ECG with ventilatory function tests in chronic obstructive lung disease (COLD) in Nigerians.
Although the most objective assessment of the severity of COLD is done by spirometer, this is not as readily available in Nigeria as the electrocardiograph, thus the ECG is often used to assess it. This study examines the relationship between the ECG findings and FEV 1 obtained by spirometry and expressed as a proportion predicted for age and sex in 92 Nigerians with COLD of which 39 had associated pulmonate. There was an inverse relationship between the mean electrical axis of the P wave on the ECG and the FEV 1 of predicted. The axis was more positive (82 +/- 12 degrees) among those with FEV 1 less than 50% of predicted (group 1) and this decreased progressively with increasing FEV 1 to 72 +/- 14 degrees in those with FEV 1 between 50-70% (group 2) and 67 +/- 16 degrees in those with FEV 1 greater than 70% (group 3). There was also a significant relationship between FEV 1 and the development of cor pulmonale and 71.4% of those who had the lowest FEV 1 (group 1) had cor pulmonale while the proportion decreased with the reduction in the severity of airway obstruction. A rightward P wave axis greater than 80% was statistically significant associated with development of cor pulmonale (X2 = 29.5 (P < 0.001) of those with COLD and cor pulmonale, 72.2% had a P wave axis greater than 80%. Only 13.2% of those with COLD alone had a P wave axis greater than 80 degrees. Cardiac arrhythmias were present in 28 patients, ventricular (VA) in 23 cases, and atrial (AA) in 7 cases. Both AA and VA were associated with more severe airway obstruction. All 3 patients who had atrial fibrillation (AF) and FEV 1 below 50% of predicted (group 1) and had cor pulmonale while 2 of the remaining 4 with AA also were in group 1 and the remaining 2 in group 2. The distribution of ventricular arrhythmias (VA) showed that 10 (43.5%) were in group 1, 9 (39.1%) in group 2, and 2 (8.7%) in group 3. Both VA and AA were also significantly related to the development of cor pulmonale. A P wave amplitude greater than 2.5 mm was significantly related to the development of clinical cor pulmonale X2 = 24.6 P < 0.001. The results show that ECG findings correlate well with spirometric assessments of FEV 1 and clinical severity in Nigerians with COLD and are, therefore, useful where spirometry is unavailable.


Awareness as observational heterarchy.
Libet et al. (1983) revealed that brain activity precedes conscious intention. For convenience in this study, we divide brain activity into two parts: a conscious field (CF) and an unconscious field (UF). Most studies have assumed a comparator mechanism or an illusion of CF and discuss the difference of prediction and postdiction. We propose that problems to be discussed here are a twisted sense of agency between CF and UF, and another definitions of prediction and postdiction in a mediation process for the twist. This study specifically examines the definitions throughout an observational heterarchy model based on internal measurement. The nature of agency must be emergence that involves observational heterarchy. Consequently, awareness involves processes having duality in the sense that it is always open to the world (postdiction) and that it also maintains self robustly (prediction).


Differential Tolerance to FTY720-Induced Antinociception in Acute Thermal and Nerve Injury Mouse Pain Models: Role of Sphingosine-1-Phosphate Receptor Adaptation.
The immunomodulatory prodrug 2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol (FTY720), which acts as an agonist for sphingosine-1-phosphate (S1P) receptors (S1PR) when phosphorylated, is proposed as a novel pain therapeutic. In this study, we assessed FTY720-mediated antinociception in the radiant heat tail-flick test and in the chronic constriction injury (CCI) model of neuropathic pain in mice. FTY720 produced antinociception and antiallodynia, respectively, and these effects were dose-dependent and mimicked by the S1PR1-selective agonist CYM-5442. Repeated administration of FTY720 for 1 week produced tolerance to acute thermal antinociception, but not to antiallodynia in the CCI model. S1PR-stimulated [35S]GTPγS autoradiography revealed apparent desensitization of G protein activation by S1P or the S1PR1 agonist 5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole (SEW-2871) throughout the brain. Similar results were seen in spinal cord membranes, whereby the Emax value of S1PR-stimulated [35S]GTPγS binding was greatly reduced in repeated FTY720-treated mice. These results suggest that S1PR1 is a primary target of FTY720 in alleviating both acute thermal nociception and chronic neuropathic nociception. Furthermore, the finding that tolerance develops to antinociception in the tail-flick test but not in chronic neuropathic pain suggests a differential mechanism of FTY720 action between these models. The observation that repeated FTY720 administration led to desensitized S1PR1 signaling throughout the central nervous system suggests the possibility that S1PR1 activation drives the acute thermal antinociceptive effects, whereas S1PR1 desensitization mediates the following: 1) tolerance to thermal antinociceptive actions of FTY720 and 2) the persistent antiallodynic effects of FTY720 in neuropathic pain by producing functional antagonism of pronociceptive S1PR1 signaling.


Pax3 induces differentiation of juvenile skeletal muscle stem cells without transcriptional upregulation of canonical myogenic regulatory factors.
Pax3 is an essential myogenic regulator of fetal and embryonic development, but its role in postnatal myogenesis remains a topic of debate. We show that constitutive expression of Pax3 in postnatal, juvenile mouse skeletal muscle stem cells, a subset of the heterogeneous satellite cell pool highly enriched for myogenic activity, potently induces differentiation. This differentiation-promoting activity stands in contrast to the differentiation-inhibiting effects of Pax3 in the commonly used mouse myoblast cell line C2C12. Pax3 mRNA levels in distinct muscles correlate with the rate of myogenic differentiation of their muscle stem cells. Although Pax3 controls embryonic myogenesis through regulation of the canonical myogenic regulatory factors (MRFs) Myf-5, MyoD, myogenin and Mrf4, we find that in postnatal muscle stem cells, ectopic Pax3 expression fails to induce expression of any of these factors. Unexpectedly, overexpression of neither Myf-5 nor myogenin is sufficient to induce differentiation of juvenile stem cells; and knockdown of Myf-5, rather than inhibiting differentiation, promotes it. Taken together, our results suggest that there are distinct myogenic regulatory pathways that control the embryonic development, juvenile myogenesis and adult regeneration of skeletal myofibers.


The Neural Systems of Forgiveness: An Evolutionary Psychological Perspective.
Evolution-minded researchers posit that the suite of human cognitive adaptations may include forgiveness systems. According to these researchers, forgiveness systems regulate interpersonal motivation toward a transgressor in the wake of harm by weighing multiple factors that influence both the potential gains of future interaction with the transgressor and the likelihood of future harm. Although behavioral research generally supports this evolutionary model of forgiveness, the model's claims have not been examined with available neuroscience specifically in mind, nor has recent neuroscientific research on forgiveness generally considered the evolutionary literature. The current review aims to help bridge this gap by using evolutionary psychology and cognitive neuroscience to mutually inform and interrogate one another. We briefly summarize the evolutionary research on forgiveness, then review recent neuroscientific findings on forgiveness in light of the evolutionary model. We emphasize neuroscientific research that links desire for vengeance to reward-based areas of the brain, that singles out prefrontal areas likely associated with inhibition of vengeful feelings, and that correlates the activity of a theory-of-mind network with assessments of the intentions and blameworthiness of those who commit harm. In addition, we identify gaps in the existing neuroscientific literature, and propose future research directions that might address them, at least in part.


Effects of risedronate on bone turnover markers in osteoporotic postmenopausal women: comparison of two protocols of treatment.
Bisphosphonates are powerful agents able to prevent bone loss. The objective of the study was to evaluate the efficacy and tolerability of risedronate once a week (35 mg) compared with risedronate 5 mg once daily in women with osteoporosis. A randomized, double-blind, active-controlled study enrolled 102 postmenopausal women aged 66.5+/-7.5 years with osteoporotic fractures. All women received risedronate during 6 months. Group 1 (G1, n=51) received risedronate 5 mg once daily and group 2 (G2, n=51) received 35 mg once a week. Serum alkaline phosphatase (ALP), bone alkaline phosphatase (bone ALP), serum C-terminal telopeptide of type I collagen (CTX) were measured at baseline, 3 months and 6 months after treatment in the two groups. We noted no significant difference in markers between women of the 2 groups. After 3 months, bone ALP and CTX decreased (respectively -22.1% and -47.6%) in the 2 groups with no significant difference between them. After 6 months study, bone ALP and CTX decreased respectively by -46.5% and -62.9% with no statistically significant difference between study groups for bone markers. Our study found that treatment with once weekly risedronate 35 mg is able to decrease CTX and bone ALP compared with risedronate 5 mg once daily, in postmenopausal women with osteoporotic fractures. We didn't find adverse events with the 35 mg once-a-week dose group compared to the once-daily dose group. Based on these results, the effects of risedronate 35 mg once a week are similar in efficacy to daily dosing and may lead less adverse events than once-a-month dose. This therapeutic protocol may provide an alternative for patients who prefer once-a-week oral dosing.


A New Proposal for Learning Curve of TEP Inguinal Hernia Repair: Ability to Complete Operation Endoscopically as a First Phase of Learning Curve.
Background. The exact nature of learning curve of totally extraperitoneal inguinal hernia and the number required to master this technique remain controversial. Patients and Methods. We present a retrospective review of a single surgeon experience on patients who underwent totally extraperitoneal inguinal hernia repair. Results. There were 42 hernias (22 left- and 20 right-sided) in 39 patients with a mean age of 48.8 ± 15.1 years. Indirect, direct, and combined hernias were present in 18, 12, and 12 cases, respectively. The mean operative time was 55.1 ± 22.8 minutes. Peritoneal injury occurred in 9 cases (21.4%). Conversion to open surgery was necessitated in 7 cases (16.7%). After grouping of all patients into two groups as cases between 1-21 and 22-42, it was seen that the majority of peritoneal injuries (7 out of 9, 77.8%, P = 0.130) and all conversions (P = 0.001) occurred in the first 21 cases. Conclusions. Learning curve of totally extraperitoneal inguinal hernia repair can be divided into two consequent steps: immediate and late. At least 20 operations are required for gaining anatomical knowledge and surgical pitfalls based on the ability to perform this operation without conversion during immediate phase.


Amino acid supplements and metabolic health: a potential interplay between intestinal microbiota and systems control.
Dietary supplementation of essential amino acids (EAAs) has been shown to promote healthspan. EAAs regulate, in fact, glucose and lipid metabolism and energy balance, increase mitochondrial biogenesis, and maintain immune homeostasis. Basic science and epidemiological results indicate that dietary macronutrient composition affects healthspan through multiple and integrated mechanisms, and their effects are closely related to the metabolic status to which they act. In particular, EAA supplementation can trigger different and even opposite effects depending on the catabolic and anabolic states of the organisms. Among others, gut-associated microbial communities (referred to as gut microbiota) emerged as a major regulator of the host metabolism. Diet and host health influence gut microbiota, and composition of gut microbiota, in turn, controls many aspects of host health, including nutrient metabolism, resistance to infection, and immune signals. Altered communication between the innate immune system and the gut microbiota might contribute to complex diseases. Furthermore, gut microbiota and its impact to host health change largely during different life phases such as lactation, weaning, and aging. Here we will review the accumulating body of knowledge on the impact of dietary EAA supplementation on the host metabolic health and healthspan from a holistic perspective. Moreover, we will focus on the current efforts to establish causal relationships among dietary EAAs, gut microbiota, and health during human development.


cot1: a regulator of Arabidopsis trichome initiation.
In Arabidopsis, the timing and spatial arrangement of trichome initiation is tightly regulated and requires the activity of the GLABROUS1 (GL1) gene. The COTYLEDON TRICHOME 1 (COT1) gene affects trichome initiation during late stages of leaf development and is described in this article. In the wild-type background, cot1 has no observable effect on trichome initiation. GL1 overexpression in wild-type plants leads to a modest number of ectopic trichomes and to a decrease in trichome number on the adaxial leaf surface. The cot1 mutation enhances GL1-overexpression-dependent ectopic trichome formation and also induces increased leaf trichome initiation. The expressivity of the cot1 phenotype is sensitive to cot1 and 35S::GL1 gene dosage, and the most severe phenotypes are observed when cot1 and 35S::GL1 are homozygous. The COT1 locus is located on chromosome 2 15.3 cM north of er. Analysis of the interaction between cot1, try, and 35S::GL1 suggests that COT1 is part of a complex signal transduction pathway that regulates GL1-dependent adoption of the trichome cell fate.


The Importance of Cystoscopy in Diagnosis and Treatment of Urethral Stricture Following Transurethral Prostatectomy.
Transurethral prostatectomy is the gold standard surgical treatment of bladder outlet obstruction due to benign enlargement of the prostate, with more than 30,000 procedures performed annually in the United States alone. The success rate of this minimally invasive procedure is high and the results are durable. The development of urethral stricture is a long-term complication of the procedure and is noted in about 2% of patients. The stricture narrows the urethral lumen, leading to re-appearance of obstructive urinary symptoms. Traditionally, the evaluation of the stricture was performed by retrograde urethrography. Advancements in the fields of flexible endoscopy allowed rapid inspection of the urethra and immediate dilatation of the stricture in selected cases. To compare the efficacy of urethrography versus cystoscopy in the evaluation of urethral strictures following transurethral prostatectomy. A retrospective review was conducted of a series of 32 consecutive patients treated due to post-transurethral resection of prostate (TURP) urethral stricture. Twenty patients underwent both tests. In 16 there was concordance between the two tests. Four patients had no pathological findings in urethrography but had strictures in cystoscopy. All strictures were short (up to 10 mm) and were easily treated during cystoscopy, with no complaints or re-surgery needed in 24 months follow-up. Cystoscopy was superior to urethrography in the evaluation of post-TURP strictures. Strictures where often short and treated during the same procedure. We recommend that cystoscopy be the procedure of choice in evaluating obstructive urinary symptoms after TURP, and retrograde urethrography be preserved for selected cases.


Tigroid pattern of cerebral white matter involvement in chromosome 6p25 deletion syndrome with concomitant 5p15 duplication.
Sub-telomeric deletions of the short arm of chromosome 6 are a well-described clinical entity characterized by developmental impairment, hypotonia, eye abnormalities and defects in the heart and kidneys. Chromosome 5p terminal duplication is a rarer entity, associated with developmental impairment and facial dysmorphism. We report a 3-year-old patient with a chromosome 6p25.1pter deletion and chromosome 5p15.1pter duplication who had global developmental impairment and unusual cerebral white matter changes, with hypoplastic corpus callosum and cerebellar vermis on magnetic resonance imaging -brain scan. We discuss the differential diagnosis to consider in patients with this appearance on magnetic resonance imaging -brain scan and reiterate the need for chromosome analysis in patients with this pattern of developmental anomaly. Tigroid pattern of cerebral white matter involvement has not been reported in chromosomal deletion/duplication syndromes. With the increasing use of molecular karyotyping for patients with multiple congenital anomalies and developmental delay, it is important to consider the exact size and nature of chromosomal deletion/duplication, in order to provide families with prognostic information and recurrence risk. This in turn, will help provide valuable information regarding the natural history of rare chromosomal imbalances.


Limited Unfolded Protein Response and Inflammation in Neuroserpinopathy.
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a rare disease characterized by the deposition of multiple intracytoplasmic neuronal inclusions that contain mutated neuroserpin. Tg-Syracuse (Tg-Syr) mice express Ser49Pro mutated neuroserpin and develop clinical and neuropathological features of human FENIB. We used 8-, 34-, 45- and 80-week-old Tg-Syr mice to characterize neuroinflammation and the unfolded protein response (UPR) in a neurodegenerative disease in which abnormal protein aggregates accumulate within the endoplasmic reticulum (ER). There were scattered neuroserpin inclusions in Tg-Syr mice at 8 weeks of age; the numbers of neurons involved and the amount of neuroserpin per neuron increased with age throughout the CNS to 80 weeks of age; no similar inclusions were found in wild type (Tg-WT) mice at any age. Increases in numbers of astrocytes and microglia occurred at advanced disease stages. Among 22 markers in 80-week-old Tg-Syr mice, only II1b and II10rb mRNAs in the somatosensory cortex and CxCl10 and Il10rb mRNAs in the olfactory bulb were upregulated when compared with Tg-WT mice indicating a limited relationship between neuroserpin inclusions and inflammatory responses. The changes were accompanied by a transient increase in expression of Xbp1 spliced at 45 weeks and increased ERdJ4 mRNAs at 80 weeks. The sequestration of UPR activators GRP78 and GRP94 in neuroserpin inclusions might explain the limited UPR responses despite the accumulation of neuroserpin in the ER in this FENIB mouse model.


Cognitive self-regulation influences pain-related physiology.
Cognitive self-regulation can shape pain experience, but its effects on autonomic responses to painful events are unclear. In this study, participants (N = 41) deployed a cognitive strategy based on reappraisal and imagination to regulate pain up or down on different trials while skin conductance responses (SCRs) and electrocardiogram activity were recorded. Using a machine learning approach, we first developed stimulus-locked SCR and electrocardiogram physiological markers predictive of pain ratings. The physiological markers demonstrated high sensitivity and moderate specificity in predicting pain across 2 data sets, including an independent test data set (N = 84). When we tested the markers on the cognitive self-regulation data, we found that cognitive self-regulation had significant impacts on both pain ratings and pain-related physiology in accordance with regulatory goals. These findings suggest that self-regulation can impact autonomic nervous system responses to painful stimuli and provide pain-related autonomic profiles for future studies.


Discovery and development of educational strategies to encourage safe food handling behaviors in cancer patients.
Foodborne infections pose a threat to cancer patients who are immunocompromised because of disease or medical therapy. Comprehensive food safety education can raise cancer patients' awareness of risk for foodborne infections and encourage risk-reducing behavior. The objectives of this study were to assess food safety informational needs of cancer patients and to determine factors that may influence prospective educational interventions that foster risk-reducing behaviors. Focus groups with cancer patients were formed, and interviews with health professionals working with cancer patients were conducted. Findings were used to develop three educational resource prototypes for cancer patients. Information from two additional focus groups and interviews with cancer patients was used to evaluate the prototypes before revision and finalization. There was a general awareness among focus group participants that chemotherapy increased their susceptibility to foodborne illness and infections. Participants had a basic knowledge of safe food handling practices but did not necessarily link their awareness of increased susceptibility for infection with their routine food handling practices. When informed of specific high-risk foods, there was skepticism about compliance due to disbelief of the risk, personal preferences for the high-risk food, and lack of information about how to use the recommendation. Most of the health care providers agreed that food safety information should be provided by dietitians, physicians, and nurses, but physicians stated they had little time to do so. Cancer patients expressed positive attitudes toward the educational resource prototypes and willingness to follow the food safety recommendations provided.


Tough, sticky and remoldable hydrophobic association hydrogel regulated by polysaccharide and sodium dodecyl sulfate as emulsifiers.
Hydrophobic association hydrogels have been extensively studied during the past decades. However, the fracture stress of hydrophobic association hydrogels obtained with anionic surfactants (such as sodium dodecyl sulfate) achieved hundreds of Pascal. In this investigation, combined surfactants consisting of polysaccharide (gum arabic) and sodium dodecyl sulfate were utilized to stabilize hydrogels with high fracture stress of more than 1 MPa. Moreover, the hydrogels exhibited excellent self-healing capacity and remoldable behavior without any stimulation. Simultaneously, the hydrogels demonstrated an adhesive behavior for various solid substrates including polytetrafluoroethylene, plastics, rubbers, glasses, metals and woods. The hydrogel with toughness, self-healing, stickiness and remoldable properties would be expected to be applied in the medical fields, such as wound dressing, medical electrodes, tissue adhesives and portable equipment.


Psychoanalysis and Eastern spiritual healing traditions.
An exploration of the theory and practice of healing in the Eastern spiritual traditions reveals the centrality of the idealizing transference in the patient-seeker's interaction with the spiritual teacher or the guru although the aim and development of the idealizing transference in the spiritual traditions are quite different from those of self psychology. In its emphasis on the guru's empathy and in claiming that its meditative practices radically reduce the noise and glare produced by the sensual self which is the chief obstacle to the teacher-healer's empathic understanding of the patient, the Eastern healing discourse goes considerably beyond most traditional psychoanalytic formulations on the nature and communication of empathy in the analytic situation. The Eastern traditions' claim of a significant enhancement of the teacher-healer's empathic capacity through meditative practices, and its communication to the patient/seeker through other channels besides the verbal one, can make an important contribution to the discussion on the role of empathy in psychoanalytic discourse and, if the claim proves true, to a place for meditative practices in psychoanalytic education.


[Protein-energy malnutrition in clinical practice].
The analysis of the reasons and mechanisms of development of an protein-energy malnutrition, communication of fetal pathology and development of an protein-energy malnutrition at mature age is submitted. Systemic character of a syndrome is marked out. Importance of a problem of an protein-energy malnutrition at patients with a dysplasia of a connecting tissue is bound to high prevalence of a syndrome at this pathology.


Carriage of multidrug-resistant carbapenemase-producing gram-negative bacteria in patients admitted to NHS Greater Glasgow and Clyde hospitals: Implications for treatment.
Infections caused by gram-negative carbapenemase-producing organisms (CPO) have become a global phenomenon. Screening of patients for CPO that was carried out at 48-h intervals enables early detection of carriers for infection control purposes and planning therapy. We investigated the bacterial flora detected on screening, the enzymes that conferred resistance and the proportion of patients who developed bacteraemia with CPO and their therapy. In all, 27 patients had a positive screen for CPO. A small but significant (7.5%) proportion of patients were not detected on initial screening. Escherichia coli and Klebsiella were predominant. New-Delhi metallo β-lactamase and oxacillin carbapenemases were the main enzymatic mechanisms of resistance. Four (14.8%) patients developed bacteraemia with CPO (30- and 90-day survival 100% and 75%, respectively). A single negative screen does not rule out colonisation. A significant proportion of patients colonised with CPO develop bacteraemia. Vigilance is needed to prevent the nosocomial spread of CPO.


Radial matrix constraint influences tissue contraction and promotes maturation of bi-layered skin equivalents.
Human skin equivalents (HSEs) serve as important tools for mechanistic studies with human skin cells, drug discovery, pre-clinical applications in the field of tissue engineering and for skin transplantation on skin defects. Besides the cellular and extracellular matrix (ECM) components used for HSEs, physical constraints applied on the scaffold during HSEs maturation influence tissue organization, functionality, and homogeneity. In this study, we introduce a 3D-printed culture insert that exposes bi-layered HSEs to a static radial constraint through matrix adhesion. We examine the effect of various diameters of the ring-shaped culture insert on the HSE's characteristics and compare them to state-of-the-art unconstrained and planar constrained HSEs. We show that radial matrix constraint of HSEs regulates tissue contraction, promotes fibroblast and matrix organization that is similar to human skin in vivo and improves keratinocyte differentiation, epidermal stratification, and basement membrane formation depending on the culture insert diameter. Together, these data demonstrate that the degree of HSE's contraction is an important design consideration in skin tissue engineering. Therefore, this study can help to mimic various in vivo skin conditions and to increase the control of relevant tissue properties.


Cohort size and age-specific suicide rates: a contingent relationship.
Trends in age-specific suicide rates relate to debates about the consequences of population aging and changes in cohort size for social well-being. Easterlin argues that large cohort size increases suicide rates by reducing relative income; Preston claims that suicide rates fall in large cohorts with high levels of political and social power. To integrate these competing arguments, this paper uses aggregate data on 18 high-income nations from 1953 to 1986 to demonstrate that the direction and strength of the relationship between cohort size and suicide depend on (1) age of the cohort, (2) gender, (3) national context, and (4) time period. The results show that large cohort size raises suicide for the young and middle-aged, but reduces it for the elderly. Also, the effects of cohort size prove stronger for men than for women, for nations with less collectivist institutions than for nations with more collectivist institutions, and for the 1950s and 1960s than for the 1970s and 1980s.


redLips: a comprehensive mechanistic model of the lipid metabolic network of yeast.
Over the last decades, yeast has become a key model organism for the study of lipid biochemistry. Because the regulation of lipids has been closely linked to various physiopathologies, the study of these biomolecules could lead to new diagnostics and treatments. Before the field can reach this point, however, sufficient tools for integrating and analyzing the ever-growing availability of lipidomics data will need to be developed. To this end, genome-scale models (GEMs) of metabolic networks are useful tools, though their large size and complexity introduces too much uncertainty in the accuracy of predicted outcomes. Ideally, therefore, a model for studying lipids would contain only the pathways required for the proper analysis of these biomolecules, but would not be an ad hoc reduction. We hereby present a metabolic model that focuses on lipid metabolism constructed through the integration of detailed lipid pathways into an already existing GEM of Saccharomyces cerevisiae. Our model was then systematically reduced around the subsystems defined by these pathways to provide a more manageable model size for complex studies. We show that this model is as consistent and inclusive as other yeast GEMs regarding the focus and detail on the lipid metabolism, and can be used as a scaffold for integrating lipidomics data to improve predictions in studies of lipid-related biological functions.


THE RELATION OF INFLAMMATION TO THE MOLECULAR STRUCTURE OF CARBON COMPOUNDS SOLUBLE IN THE FLUIDS OF THE BODY.
The peritoneal, like the pleural cavity, gives opportunity to measure with adequate accuracy the activity of inflammatory reactions defined by movement of fluid within the cavity, by migration of leucocytes into it, and by exudation of proteins from the plasma. The activity of inflammatory reactions caused by saccharides or by alcohols that were tested varied in accord with their molecular weight, the osmotic pressure maintained by solutions of corresponding concentration, their boiling point, or by other colligative properties. Blood serum or globulin in the concentration with which it occurs in blood serum injected into the peritoneal cavity caused changes which differed little from those caused by physiological salt solution. Protein with molecular weight as low as that of cytochrome C (12,000) or ovalbumin (45,000) when in dilute solution (1 per cent) were rapidly absorbed, whereas trypsin and chymotrypsin under the same conditions caused very active inflammatory reactions because they set free amino acids and perhaps polypeptides with amino acids in short chains. The activity of inflammatory reactions caused by carbon compounds soluble in body fluids varied in accord with their colligative properties.


Parainfluenza virus 5 m protein interaction with host protein 14-3-3 negatively affects virus particle formation.
Paramyxovirus matrix (M) proteins organize virus assembly, linking viral glycoproteins and viral ribonucleoproteins together at virus assembly sites on cellular membranes. Using a yeast two-hybrid screening approach, we identified 14-3-3 as a binding partner for the M protein of parainfluenza virus 5 (PIV5). Binding in both transfected and PIV5-infected cells was confirmed by coimmunoprecipitation and was mapped to a C-terminal region within the M protein, namely, 366-KTKSLP-371. This sequence resembles known 14-3-3 binding sites, in which the key residue for binding is a phosphorylated serine residue. Mutation of S369 within the PIV5 M protein disrupted 14-3-3 binding and improved the budding of both virus-like particles (VLPs) and recombinant viruses, suggesting that 14-3-3 binding impairs virus budding. 14-3-3 protein overexpression reduced the budding of VLPs. Using (33)P labeling, phosphorylated M protein was detected in PIV5-infected cells, and this phosphorylation was nearly absent in cells infected with a recombinant virus harboring an S369A mutation within the M protein. Assembly of the M protein into clusters and filaments at infected cell surfaces was enhanced in cells infected with a recombinant virus defective in 14-3-3 binding. These findings support a model in which a portion of M protein within PIV5-infected cells is phosphorylated at residue S369, binds the 14-3-3 protein, and is held away from sites of virus budding.


[Application of methylation-specific multiplex ligation-dependent probe amplification for the study of DNA methylation in placenta tissues].
To study the feasibility of using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) for the detection of DNA methylation in placenta tissue. For blood cells from 13 non-pregnant women and 9 euploid placenta, the ratios of DNA methylation were evaluated for 4 genes including CGI149, CGI113, HLCS and ACTB with MS-MLPA and bisulfite sequencing, respectively. The methylation ratio of the ACTB gene was 0-0.1 for the blood cells when the digestion control was completely digested. The cutoff value for the methylation ratio of MS-MLPA has been determined as 0.1. For the 9 placenta samples, results of MS-MLPA and bisulfite sequencing were concordant for all of the four genes. MS-MLPA is an effective alternative to bisulfite sequencing for the assessment of methylation ratios in placental tissues.


Influence of organ environment on the growth, selection, and metastasis of human colon carcinoma cells in nude mice.
The purpose of these studies was to determine whether the biological and metastatic behaviors of tumor cells isolated from fresh surgical specimens of human colon carcinomas are influenced by the isolation method and the organ site of implantation and growth in nude mice. Three surgical specimens were obtained from three different patients. Two tumors were primary human colorectal carcinomas (HCC) classified as Dukes' B2 (KM12) and Dukes' D stages (KM20), and the third was from a liver metastasis (KM23). The tumors were enzymatically dissociated, and viable cells were implanted into the subcutis or spleen of different nude mice or were established in culture. Tumors developed in both sites of implantation, but hepatic metastases were found only in those nude mice that received splenic implantations of HCC cells. Cells from Dukes' D stage tumors produced more hepatic disease than cells from the Dukes' B tumor. Cells of the parental KM12C (culture) were injected into the spleen or cecum of nude mice to produce experimental and spontaneous hepatic metastases, respectively. HCC lesions were harvested from livers of nude mice and established as individual cell lines in culture. This procedure yielded cell lines KM12SM (spontaneous metastasis) and KM12L1 (experimental metastasis). The selection cycle for cells implanted into the spleen was repeated three more times to produce the cell line designated KM12L4. Cells of the parental KM12C and the three selected variants were injected into nude mice by different routes: i.v., s.c. into the cecum, and into the spleen. Subsequent to implantation into the spleen, all cell lines were shown to be tumorigenic. Cells from the selected KM12L4 and KM12SM lines produced a significantly higher number of experimental liver metastases than the parental cells. Moreover, subsequent to the injection into the cecum, cells of the once-selected KM12SM (for spontaneous metastasis) produced a higher incidence of spontaneous liver metastasis than all other lines. The human origin of all the lines was confirmed by isoenzyme and karyotype analyses. The two highly metastatic lines (KM12L4 and KM12SM) were tetraploid and produced elevated levels of type IV collagenolytic activity. Collectively, the results demonstrate that the orthotopic implantation of HCC cells into the appropriate organ environment can be used for efficient isolation and for study of metastatic subpopulations of cells from human colon carcinoma.


Physical and chemical conditions for microbial oil degradation.
Oil residues arising from the Christos-Bitas spillage were found to contain 28% of oil extractable by carbon tetrachloride; the remainder comprised water and undefined solids. When incubated in 8-L rectangular tanks with a mixed population of mainly bacteria to which diammonium hydrogen phosphate was added, ca. 97% of the Christos-Bitas oil fraction was degraded. When the same substrate was degraded by only three isolated Pseudomonas strains in 1-L cylindrical tanks, degradation was only ca. 56%. Raising the temperature from 20 to 50 degrees C brought about a visible loss in cell viability with only ca. 38% of the substrate degraded. Oil degradation proceeded in direct proportion to increases in cell attachment to the dispersed oil. The aliphatic fraction of Kuwait crude oil up to nC(25) measured by gas liquid chromatography (GLC) was oxidized within 48 h. Using this substrate the three pseudomonads together brought about a more complete degradation (87%) than a single Bacillus isolate. The Bacillusstrain was capable of deggrading between 50 and 65% of the crude, depending on whether diammonium hydrogen phosphate supplemented a peptone-based medium. The preferential biodgradability of fractions was the following aliphatics > aromatics > asphalts, as has been widely reported.


Deep Learning-Based Remaining Useful Life Estimation of Bearings with Time-Frequency Information.
In modern industrial production, the prediction ability of remaining useful life of bearings directly affects the safety and stability of the system. Traditional methods require rigorous physical modeling and perform poorly for complex systems. In this paper, an end-to-end remaining useful life prediction method is proposed, which uses short-time Fourier transform (STFT) as preprocessing. Considering the time correlation of signal sequences, a long and short-term memory network is designed in CNN, incorporating the convolutional block attention module, and understanding the decision-making process of the network from the interpretability level. Experiments were carried out on the 2012PHM dataset and compared with other methods, and the results proved the effectiveness of the method.


B-lymphocyte signalling abnormalities and lupus immunopathology.
Lupus is a complex autoimmune rheumatic disease of unknown aetiology. The disease is associated with diverse features of immunological abnormality in which B-lymphocytes play a central role. However, the cause of atypical B-lymphocyte responses remains unclear. In this article, we provide a synopsis of current knowledge on intracellular signalling abnormalities in B-lymphocytes in lupus and their potential effects on the response of these cells in mouse models and in patients. There are numerous reported defects in the regulation of intracellular signalling proteins and pathways in B-lymphocytes in lupus that, potentially, affect critical biological responses. Most of the evidence for these defects comes from studies of disease models and genetically engineered mice. However, there is also increasing evidence from studying B-lymphocytes from patients and from genome-wide linkage analyses for parallel defects to those observed in mice. These studies provide molecular and genetic explanations for the key immunological abnormalities associated with lupus. Most of the new information appears to relate to defects in intracellular signalling that impact B-lymphocyte tolerance, cytokine production and responses to infections. Some of these abnormalities will be discussed within the context of disease pathogenesis.


[Motor neglect: issues and prospects].
Although the motor and sensory components of the neglect syndrome appear as dependent on a unitary attentional process, the clinical observation of pure motor neglect raises the possibility of segregation between attentional and intentional neural mechanisms. Neuroanatomical evidence suggests a separate role for the anterior and posterior cingulum. The anterior cingulum mainly projects to the supplementary motor area, the superior premotor area and the prefrontal granular cortex whereas the posterior cingulum mainly controls the inferior parietal lobule. The role of the intralaminar thalamic nuclei, together with the frontostriatal loops is considered. Behavioral neurology should strengthen its analytical approach in order to dissociate, by appropriate testing, the separate operations which contribute to relate perception and action. Several new hypotheses are presented.


Polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.
About 5% of schoolchildren have a specific learning disorder, defined as an unexpected failure to acquire adequate abilities in reading, writing or mathematic skills not as a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular omega-3 and omega-6 fatty acids, which are found abundantly in the brain and retina are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities. To assess the effects of polyunsaturated fatty acids (PUFAs) supplementation for children with specific learning disorders, on learning outcomes. We searched the following databases in April 2012: CENTRAL (2012, Issue 4), MEDLINE (1948 to April Week 2 2012), EMBASE (1980 to 2012 Week 16), PsycINFO (1806 to April 2012), ERIC (1966 to April 2012), Science Citation Index (1970 to 20 April 2012), Social Science Citation Index (1970 to 20 April 2012), Conference Proceedings Citation Index-Science (1970 to 20 April 2012), Conference Proceedings Citation Index-Social Sciences and Humanites (1970 to 20 April 2012), Cochrane Database of Systematic Reviews (2012, Issue 4), DARE (2012, Issue 2) , ZETOC (24 April 2012) and WorldCat (24 April 2012). We searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov on 24 April 2012. We also searched the reference lists of relevant articles identified by the searches. Randomised or quasi-randomised controlled trials comparing polyunsaturated fatty acids (PUFAs) with placebo or no treatment in children aged below 18 years with specific learning disabilities diagnosed using DSM-IV, ICD-10 or equivalent criteria. We intended to include participants with co-existing developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism. Two authors (ML and KH) independently screened the titles and abstracts of the search results and eliminated all studies that did not meet the inclusion criteria. Authors were contacted for missing information and clarifications when needed. We did not find any studies suitable for inclusion in the review. One study is awaiting classification as we were unable to get any information from the study author. There is insufficient evidence to draw any conclusion about the use of PUFAs for children with specific learning disorders. There is a need for well designed randomised studies to support or refute the use of PUFAs in this group of children.


Biocompatibility and immunologic properties of pericardial tissue stabilized by dye-mediated photooxidation.
Bovine and porcine pericardial tissues stabilized by dye-mediated photooxidation have found application as bioprosthetic heart valve material. To help predict clinical performance, a series of tests were performed to assess the biocompatibility and immunologic properties of these materials. Photooxidized bovine or porcine pericardium sterilized with an iodine-based solution were found to be non-cytotoxic, non-hemolytic, and non-mutagenic. Oil or saline extracts of these tissues passed tests for intracutaneous toxicity (irritation), acute systemic toxicity, and subchronic toxicity. Histopathology of 90-day implants of these tissues in the rabbit model demonstrated no significant macroscopic reaction and only slight microscopic response. Using a rabbit model to assess immune response, both bovine and porcine pericardial tissues elicited low levels of antibody. Furthermore, tissue photooxidation or iodine sterilization did not increase the overall level of antibodies. Glutaraldehyde-treated tissue also elicited low antibody levels which were higher than photooxidized tissue-induced levels. Absorption studies indicated that the photooxidation process may generate new epitopes, possibly collagen cross-links. Using the juvenile sheep model to assess in vivo performance, bioprosthetic valves made with photooxidized tissue were implanted and allowed to serve as functional implants for up to two years. Upon explant, the photooxidized pericardial leaflets were found to be non-calcific and partially covered with a layer of host cells. Histological cross-sections stained with von Willebrand's factor confirmed this layer as endothelial cells.


Changing Trend of Superficial Mycoses with Increasing Nondermatophyte Mold Infection: A Clinicomycological Study at a Tertiary Referral Center in Assam.
Superficial mycosis is the commonest infections affecting human globally. Though they do not cause mortality, their clinical significance lies in their morbidity, recurrence, and cosmetic disfigurement, thus creating a major public health problem. The infections are more prevalent in the tropical regions. The etiological agents are also seen to vary with time and geographical location. This study was carried out to find out the trend of superficial mycosis in Assam, along with a clinicomycological correlation. A total of 130 clinically diagnosed cases of superficial mycoses attending the outpatient department (OPD) of a tertiary hospital in Assam for a period of 1 year were taken up for the study. After taking the informed consent and a proper history, the clinical materials like skin scrapings, nail clippings, and infected hair were sent for mycological examination. The infection was found to be more prevalent among males than females (M:F, 3:2) and among the farmers and laborers (24.61%). Tinea corporis was the commonest clinical type (21.5%). Among the fungal isolates, dermatophytes were the most frequent isolates (43.54%), out of which Trichophyton rubrum was commonest. nondermatophyte moulds like Fusarium, Aspergillus, Scopulariopsis, Trichosporon, and Penicillium spp. were isolated. The epidemiology of fungal infection and the causative fungi is seen to vary geographically and with time. This study reflects the changing trend of fungal infection in the north eastern region with a high rate of isolation of nondermatophyte moulds as the causative agent.


Evaluation and Management of the Athlete's Hip.
Hip and groin pain is common in athletes, and there are many possible underlying pathologies. It is important to describe athletic hip pathology in the context of sport-specific physiologic loads and biomechanical demands. Three distinct types of athletes with this pathology are collision athletes, hypermobility athletes, and endurance athletes. Although there is considerable overlap between sports, athletes with hip pain should always be evaluated in the context of their sport. Understanding the effect of sport-specific biomechanical demands may help with both diagnosis and treatment of athletic hip pathology; however, each athlete's injury should be analyzed on an individual basis.


Teacher and peer reports of overweight and bullying among young primary school children.
Overweight is a potential risk factor for peer victimization in late childhood and adolescence. The current study investigated the association between BMI in early primary school and different bullying involvement roles (uninvolved, bully, victim, and bully-victim) as reported by teachers and children themselves. In a population-based study in the Netherlands, measured BMI and teacher-reported bullying behavior were available for 4364 children (mean age = 6.2 years). In a subsample of 1327 children, a peer nomination method was used to obtain child reports of bullying. In both teacher- and child-reported data, a higher BMI was associated with more victimization and more bullying perpetration. For instance, a 1-point increase in BMI was associated with a 0.05 increase on the standardized teacher-reported victimization score (95% confidence interval, 0.03 to 0.07; P < .001). Combining the victimization and bullying scores into different types of bullying involvement showed that children with obesity, but not children with overweight, had a significantly higher risk to be a bully-victim (odds ratio = 2.25; 95% confidence interval, 1.62 to 3.14) than normal-weight peers. At school entry, a high BMI is a risk factor associated with victimization and bullying perpetration, with obese children particularly likely to be victims and aggressors. Results were consistent for teacher and child reports of bullying, supporting the validity of our findings. Possibly, obesity triggers peer problems, but the association may also reflect a common underlying cause that makes obese children vulnerable to bullying involvement.


Oral Glucose Tolerance Test in Pregnancy and Subsequent Maternal Hypertension.
The aim of the study is to evaluate whether values and the shape of the glucose curve during the oral glucose tolerance test (OGTT) in pregnancy identify women at risk of developing hypertension (HTN) later in life. This category includes the secondary analysis of a follow-up from a mild gestational diabetes mellitus (GDM) study that included a treatment trial for mild GDM (n = 458) and an observational cohort of participants with abnormal 1-hour glucose loading test only (normal OGTT, n = 430). Participants were assessed at a median of 7 (IQR 6-8) years after their index pregnancy, and trained staff measured their blood pressure (systolic blood pressure [SBP]; diastolic blood pressure [DBP]). The association between values and the shape of the glucose curve during OGTT in the index pregnancy and the primary outcome defined as elevated BP (SBP ≥120, DBP ≥80 mm Hg, or receiving anti-HTN medications), and secondary outcome defined as stage 1 or higher (SBP ≥130, DBP ≥80 mm Hg, or receiving anti-HTN medications) at follow-up were evaluated using multivariable regression, adjusting for maternal age, body mass index, and pregnancy-associated hypertension during the index pregnancy. There was no association between fasting, 1-hour OGTT, and the outcomes. However, the 2-hour OGTT value was positively associated (adjusted odds ratio [aRR] per 10-unit increase 1.04, 95% CI 1.01-1.08), and the 3-hour was inversely associated (aRR per 10-unit increase 0.96, 95% CI 0.93-0.99) with the primary outcome. When the shape of the OGTT curve was evaluated, a monophasic OGTT response (peak at 1 hour followed by a decline in glucose) was associated with increased risk of elevated BP (41.3vs. 23.5%, aRR 1.66, 95% CI 1.17-2.35) and stage 1 HTN or higher (28.5 vs. 14.7%, aRR 1.83, 95% CI 1.15-2.92), compared with a biphasic OGTT response. Among persons with mild GDM or lesser degrees of glucose intolerance, the shape of the OGTT curve during pregnancy may help identify women who are at risk of HTN later in life, with biphasic shape to be associated with lower risk. · The shape of the Oral Glucose Tolerance Test curve may help identify patients who are at risk of having elevated BP or HTN 5 to 10 years following pregnancy.. · The 2-hour Oral Glucose Tolerance Test values is positively associated with elevated BP 5 to 10 years following pregnancy.. · This supports the concept of pregnancy as a window to future health and represents a potential novel biomarker for maternal cardiovascular health screening..


Mild traumatic brain injury induces pericyte detachment independent of stroke vulnerability.
Mild traumatic brain injury (mTBI) is an independent risk factor for ischemic stroke and can result in poorer outcomes- an effect presumed to involve the cerebral vasculature. Here we tested the hypothesis that mTBI-induced pericyte detachment from the cerebrovascular endothelium is responsible for worsened stroke outcomes. We performed a mild closed-head injury and/or treated C57/bl6 mice with imatinib mesylate, a tyrosine kinase inhibitor that induces pericyte detachment. The time course of pericyte detachment was assessed 7, 14, and 28 days post injury (DPI). To test the role of pericytes in TBI-induced exacerbation of ischemic stroke outcomes, we induced mTBI and/or treated mice with imatinib for one week prior to transient middle cerebral artery occlusion. We found that injury promoted pericyte detachment from the vasculature commensurate with the levels of detachment seen in imatinib-only treated animals, and that the detachment persisted for at least 14DPI, but recovered to sham levels by 28DPI. Further, mTBI, but not imatinib-induced pericyte detachment, increased infarct volume. Thus, we conclude that the transient detachment of pericytes caused by mTBI may not be sufficient to exacerbate subsequent ischemic stroke damage. These data have important implications for understanding cerebrovascular dysfunction following mTBI and potential mechanisms of increased risk for future ischemic strokes.


The Disconnection Hypothesis in Alzheimer's Disease Studied Through Multimodal Magnetic Resonance Imaging: Structural, Perfusion, and Diffusion Tensor Imaging.
According to the so-called disconnection hypothesis, the loss of synaptic inputs from the medial temporal lobes (MTL) in Alzheimer's disease (AD) may lead to reduced activity of target neurons in cortical areas and, consequently, to decreased cerebral blood flow (CBF) in those areas. The aim of this study was to assess whether hypoperfusion in parietotemporal and frontal cortices of patients with mild cognitive impairment who converted to AD (MCI-c) and patients with mild AD is associated with atrophy in the MTL and/or microstructural changes in the white matter (WM) tracts connecting these areas. We assessed these relationships by investigating correlations between CBF in hypoperfused areas, mean cortical thickness in atrophied regions of the MTL, and fractional anisotropy (FA) in WM tracts. In the MCI-c group, a strong correlation was observed between CBF of the superior parietal gyri and FA in the parahippocampal tracts (left: r = 0.90, p < 0.0001; right: r = 0.597, p = 0.024), and between FA in the right parahippocampal tract and the right precuneus (r = 0.551, p = 0.041). No significant correlations between CBF in hypoperfused regions and FA in the WM tract were observed in the AD group. These results suggest an association between perfusion deficits and altered WM tracts in prodromal AD, while microvasculature impairments may have a greater influence in more advanced stages. We did not find correlations between cortical thinning in the medial temporal lobes and decreased FA in the WM tracts of the limbic system in either group.


Residential radon and birth defects: A population-based assessment.
Associations have been reported between maternal radiation exposure and birth defects. No such studies were found on radon. Our objective was to determine if there is an association between living in areas with higher radon levels and birth defects. The Texas Birth Defects Registry provided data on all birth defects from 1999 to 2009 from the entire state. Mean radon levels by geologic region came from the Texas Indoor Radon Survey. The association between radon and birth defects was estimated using multilevel mixed effect Poisson regression. Birth defects overall were not associated with residential radon levels. Of the 100 other birth defect groups with at least 500 cases, 14 were significantly elevated in areas with high mean radon level in crude analyses, and 9 after adjustment for confounders. Cleft lip with/without cleft palate had an adjusted prevalence ratio of 1.16 per 1 picoCurie/liter (pCi/L) increase in exposure to region mean radon, 95% confidence interval, 1.08-1.26. Cystic hygroma / lymphangioma had an adjusted prevalence ratio of 1.22 per 1 pCi/L increase, 95% confidence interval, 1.02-1.46. Other associations were suggested but not as consistent: three skeletal defects, Down syndrome, other specified anomalies of the brain, and other specified anomalies of the bladder and urethra. In the first study of residential radon and birth defects, we found associations with cleft lip w/wo cleft palate and cystic hygroma / lymphangioma. Other associations were suggested. The ecological nature of this study and multiple comparisons suggest that our results be interpreted with caution.


METTL14-m6A-FOXO3a axis regulates autophagy and inflammation in ankylosing spondylitis.
The role of m6A in ankylosing spondylitis (AS) remains largely obscure. In this study, we found that m6A modification was decreased in T cells of AS, and the abnormal m6A modification was attributed to the downregulation of methyltransferase-like 14 (METTL14). METTL14 exerted a critical role in regulating autophagy activity and inflammation via targeting Forkhead box O3a (FOXO3a). Mechanistically, the loss of METTL14 decreased the expression of FOXO3a, leading to the damage of autophagic flux and the aggravation of inflammation. Inversely, the forced expression of METTL14 upregulated the expression of FOXO3a, thereby activating autophagy and alleviating inflammation. Furthermore, our results revealed that METTL14 targeted FOXO3a mRNA and regulated its expression and stability in a m6A-dependent manner. These findings uncovered the functional importance of m6A methylation mechanisms in the regulation of autophagy and inflammation, which expanded our understanding of this interaction and was critical for the development of therapeutic strategies for AS.


Evaluation of natural foci of Panstrongylus megistus in a forest fragment in Porto Alegre, State of Rio Grande do Sul, Brazil.
Panstrongylus megistus is commonly found in wild environments of the State of Rio Grande do Sul, Brazil. The aim of this study was to characterize the network of refuges used by triatomine in a forest fragment of Porto Alegre and to identify Trypanosoma cruzi infection, associated hosts and the epidemiological importance of both hosts and triatomines. Techniques including the spool-and-line method and active searching (transects) were used to identify natural foci. The food source for each triatomine was determined using the precipitin test, and the infection of marsupials was determined by xenodiagnosis. A total of 33 adults (domestic environment) and 27 nymphs (wild environment) of P. megistus were found in addition to 43 Didelphis albiventris specimens. The infection rates of triatomine adults, triatomine nymphs and opossums with T. cruzi I were 64%, 73% and 69%, respectively. Birds, rodents and opossums were the main resources used by triatomine. This work presents the first characterization of a natural focus of P. megistus in Rio Grande do Sul. The natural characteristics of this focus and its implication in the transmission of T. cruzi are discussed.


Specificity and degeneracy in peptide binding to HLA-B7-like class I molecules.
The HLA-B7-like binding supertype includes several different HLA-B molecules. Herein, the primary and secondary anchor specificities of the five most common HLA-B7-like molecules (B*0702, B*3501, B51, B*5301, and B*5401) were defined by the use of molecular binding assays, analogue peptides, and large sets of peptides corresponding to naturally occurring sequences. All five B7-like molecules analyzed preferentially bound 9-mers, with a stringent requirement for proline in position 2, while a variety of hydrophobic or aromatic residues were well tolerated at the C-terminal anchor position. Although most peptides bound in an allele-specific fashion, approximately 20% of the binders identified were degenerate and bound at least three of the five B7-like molecules analyzed with affinities of 500 nM or less. It was also noted that, in general, peptides that bind with high affinity to any given one B7-like molecule were also most frequently capable of degenerate binding. Prominent roles for secondary anchors in positions 1 and 3 were observed for most B7-like molecules, and secondary anchor motifs were utilized to derive an HLA-B7-like supermotif. The validity of this B7-like supermotif was tested by a blind prediction set. Finally, the B7-like supermotif was utilized to derive a general strategy for rationally engineering peptide analogues of naturally occurring sequences with greatly increased binding affinity and degeneracy. Such engineered supermotif binding peptides may be of significant utility in the development of peptide-based vaccines against chronic viral diseases and cancer.


Anxiety and epinephrine in multiparous women in labor: relationship to duration of labor and fetal heart rate pattern.
The duration of labor in multigravid subjects in phase 1 labor at term (from 3 to 6 cm of cervical dilatation; mean duration = 2.7 hours) was significantly related to measures of plasma epinephrine and norepinephrine obtained at the onset of the phase (n = 50). Epinephrine was significantly related to observer ratings of subject stress and the scores from the three dimensions of our self-report Labor Anxiety Inventory. The fetal heart rate pattern in phase 2 labor (7 to 10 cm of cervical dilatation; mean duration = 1.2 hours) was significantly related to phase 1 measures of epinephrine, observed stress, and two of the anxiety dimensions (n = 44 to 47). The results provide support for the hypotheses that, under normal clinical conditions, several types of patient anxiety are related to catecholamine levels and that anxiety and epinephrine are related to duration of labor and fetal well-being. The results suggest that medical/nursing evaluation and management of patient anxiety should include a self-report measure of three dimensions of anxiety (coping, safety, and pain), which are relatively independent of observed physical stress and which may relate to maternal labor progress as well as fetal heart rate pattern.